Periodic Reporting for period 1 - ArcHealth (Archaea for Human Health)
Período documentado: 2024-02-01 hasta 2025-07-31
Microorganisms, in particular bacteria, are increasingly recognized as potential probiotica or as biotherapeutics to improve human health. Microbes of the domain Archaea have, however, only marginally been investigated for this purpose, although they have a high potential in applications as probiotics on human skin and for healing processes. This is because they are generally more robust than bacteria, have relatively simple growth demands and no single pathogenic archaeon is known from archaea. Also the immune reaction towards archaea has been shown to be neglectable or relatively mild.
The objectives of this project were to isolate an archaeon in laboratory culture that naturally resides on human skin, to scale up its production and to investigate its potential as probiotic on skin or in therapeutical settings. During novel observations in this project a second goal emerged, which was to explore the potential of anaerobic archaea in cancer treatment.
The objectives of this project were to isolate an archaeon in laboratory culture that naturally resides on human skin, to scale up its production and to investigate its potential as probiotic on skin or in therapeutical settings. During novel observations in this project a second goal emerged, which was to explore the potential of anaerobic archaea in cancer treatment.
We successfully obtained an ammonia oxidizing archaeon of the genus Nitrosocosmicus in pure laboratory culture. ‘Nitrososcosmicus epidermidis’ is the first AOA isolated from human skin and prefers conditions that are relevant for growth on human skin including growth on surfaces as a biofilm, a temperature optimum of 29°C, and the ability to grow under high concentrations of ammonia or urea, as it occurs in human sweat.
The potential of this strain for wound healing and its effects on immune cells was tested. Only, N. epidermidis (and not other related archaea) led to a reproducible transient and dose-dependent increase of pro-inflammatory cytokines, mainly connected with innate immunity on murine and human macrophages. In addition we got promising indications in CAM assays for the potential of vasculogenesis important for chronic wounds, since these environments typically suffer from decreased perfusion and thereby decreased nutrient and oxygen flow and an impaired immune system. Both findings indicate a general potential for the application of skin archaea in wound healing which need to be further explored. Cell depletion assays using primary human fibroblasts, however, did not yet show significant results and need further optimization.
In addition we identified a second, anaerobic archaeon to be able to accumulate in tumor spheroids of colon and breat cancer lines. The archaea were detected via fluorescent labels and PCR and persisted for at least a week. The cells were also found in initial in vivo experiments to perform tumor homing. Subsequently, a novel, proprietary strain of the same genus was isolated which showed the same performance.
While bacterial ghosts induce activation of toll-like receptors, no such activation was observed with the archaeal strain. Hence, archaea are superior over other bacterial vectors, which have already been used for tumor targeting. This finding will be the foundation for a new project to harness these archaea for tumor treatment, either as a direct antitumoral compound, where they interact with the metabolome of the tumor, or as targeted carrier system.
The potential of this strain for wound healing and its effects on immune cells was tested. Only, N. epidermidis (and not other related archaea) led to a reproducible transient and dose-dependent increase of pro-inflammatory cytokines, mainly connected with innate immunity on murine and human macrophages. In addition we got promising indications in CAM assays for the potential of vasculogenesis important for chronic wounds, since these environments typically suffer from decreased perfusion and thereby decreased nutrient and oxygen flow and an impaired immune system. Both findings indicate a general potential for the application of skin archaea in wound healing which need to be further explored. Cell depletion assays using primary human fibroblasts, however, did not yet show significant results and need further optimization.
In addition we identified a second, anaerobic archaeon to be able to accumulate in tumor spheroids of colon and breat cancer lines. The archaea were detected via fluorescent labels and PCR and persisted for at least a week. The cells were also found in initial in vivo experiments to perform tumor homing. Subsequently, a novel, proprietary strain of the same genus was isolated which showed the same performance.
While bacterial ghosts induce activation of toll-like receptors, no such activation was observed with the archaeal strain. Hence, archaea are superior over other bacterial vectors, which have already been used for tumor targeting. This finding will be the foundation for a new project to harness these archaea for tumor treatment, either as a direct antitumoral compound, where they interact with the metabolome of the tumor, or as targeted carrier system.
We have isolated the first archaeon from human skin that is naturally found on most individuals in the human population and due to its metabolism should be beneficial as a probioticum or biotherapeutic. Secondly, we have identified an archaeon that can potentially be used as a tumor homing agent in future preclinical and clinical studies.
Competitive analyses, IP strategy and market analyses were developed and a patent has been submitted.
Competitive analyses, IP strategy and market analyses were developed and a patent has been submitted.